Grantee Research Project Results

Pathway Analysis Core

EPA Grant Number: R835737C005
Subproject: this is subproject number 005 , established and managed by the Center Director under grant R835737
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Human Models for Analysis of Pathways (H MAPs) Center
Center Director: Murphy, William L
Title: Pathway Analysis Core
Investigators: Roy, Sushmita
Institution: University of Wisconsin - Madison
EPA Project Officer: Aja, Hayley
Project Period: December 1, 2014 through November 30, 2018 (Extended to November 30, 2019)
RFA: Organotypic Culture Models for Predictive Toxicology Center (2013) RFA Text |  Recipients Lists
Research Category: Chemical Safety for Sustainability

Objective:

The overarching goal of our Pathway Analysis Core is to provide an integrated understanding of cellular response to environmental perturbations by developing novel network biology tools that are applicable to variety of cell types and tissue models. Our specific aims are to develop methods that (1) integrate temporal dynamics in regulatory network model reconstruction and (2) identify subnetworks that are perturbed under exposure to changing environmental stimuli. We will apply these methods to dissect regulatory networks of tissue and cell-type specific responses to small molecules and toxins from the central nervous system and liver hepatocyte development. Specifically, the core is developing methods to analyze data measured by the Brain MAPS and Liver MAPS projects.

Rationale:

Regulatory networks that control context-specific gene expression patterns play a critical role in processing extracellular environmental information to mount accurate downstream responses at the molecular and phenotypic level. Interrogating highthroughput regulatory genomic datasets with pathway and network analysis tools is emerging as a powerful approach to gain a systemic understanding of complex cellular responses. However, such approaches are in their infancy in the toxicology field.

Expected Results:

Successful completion of the objectives of the pathway analysis core will result in a comprehensive collection of network reconstruction and analysis tools that will support each of the proposed Projects, and will be publicly available to researchers affiliated to our center and beyond. Our tools will be applicable to a variety of biological contexts defined by the combination of small molecules (inputs) and tissues or cell types. Application of our tools to genomic datasets collected by various research projects will enable us to identify the common and unique parts of regulatory networks that are activated under different biological contexts. Prioritization of network nodes for downstream functional studies will greatly accelerate discovery of key nodes, including potential biomarkers for a particular biological process.

Publications and Presentations:

Publications have been submitted on this subproject: View all 17 publications for this subproject | View all 215 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 8 journal articles for this subproject | View all 81 journal articles for this center

Progress and Final Reports:

2015 Progress Report

2016 Progress Report

2017 Progress Report

2018

Final Report

Main Center Abstract and Reports:

R835737    Human Models for Analysis of Pathways (H MAPs) Center

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R835737C001 Liver MAPs
R835737C002 Brain MAPs
R835737C003 Cancer MAPs: A 3D Organotypic Microfluidic Culture System to Identify Chemicals that Impact Progression and Development of Breast Cancer
R835737C004 Vascular MAPs: Vascular and Neurovascular Tissue Models
R835737C005 Pathway Analysis Core